Our group has had a continuing interest in developing approaches to understanding and control of latent viruses through both chemotherapeutics and augmentation of natural host defenses. Viruses of special interest are cytomegalovirus (CMV) and Epstein-Barr virus. These herpes viruses lack their own thymidine kinase activity, and are not at present subject to selective antiviral therapy. We are currently studying CMV infections in immunosuppressed patient populations who are readily available for study and in whom this virus is a major source of morbidity and mortality (heart transplant recipients, cancer patients and homosexuals, etc.). Our short term efforts are directed towards three goals: 1) to improve rapidity of diagnosis and the monitoring of viral infection through the use of a filter DNA hybridization assay for virus in body fluids and a radioimmunossay for IgG and IgM antibodies; 2) to determine which cellular and or/humoral immunodeficiencies underly CMV disease severity in the immunosuppressed; and 3) to evaluate antiviral therapy and prophylaxis with various interferons, hyperimmune globulin, and those chemicals with in vitro activity against CMV (adenine arabinoside etc.). These studies will be conducted in a variety of populations including patients receiving immunosuppressive therapy and previously healthy patients with CMV infection. Long term goals include identification and characterization of the viral glycoproteins essential for immunity, both for immunoprophylaxis of individuals at high risk for CMV disease and for understanding the generation of protective immune responses in CMV infection. In a second series of experiments we want to continue our studies of the antiviral and non-antiviral actions of interferon as they can be assessed in vitro in cloned tumor cells and in vivo, in humans with disease. In vitro we are studying 1) cell surface; 2) antiproliferative; 3) antiviral and 4) intracellular enzymatic changes as they relate to the cell cycle and other growth factors. In vivo, we shall continue to study immune changes produced by interferon. Both these approaches have fundamental as well as applied implications.